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Journal of Virology, January 2003, p. 25-36, Vol. 77, No. 1
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.1.25-36.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Characterization of a Siberian Virus Isolated from a Patient with Progressive Chronic Tick-Borne Encephalitis

T. S. Gritsun,1 T. V. Frolova,2 A. I. Zhankov,3 M. Armesto,1 S. L. Turner,1 M. P. Frolova,2 V. V. Pogodina,2 V. A. Lashkevich,2 and E. A. Gould1*

CEH Institute of Virology and Environmental Microbiology, Oxford OX1 3SR, United Kingdom,1 The Chumakov Institute of Poliomyelitis and Viral Encephalitis, Moscow,2 The Mental Health Research Institute, Tomsk, Russia3

Received 15 July 2002/ Accepted 23 September 2002

A strain of Tick-borne encephalitis virus designated Zausaev (Za) was isolated in Siberia from a patient who died of a progressive (2-year) form of tick-borne encephalitis 10 years after being bitten by a tick. The complete genomic sequence of this virus was determined, and an attempt was made to correlate the sequence with the biological characteristics of the virus. Phylogenetic analysis demonstrated that this virus belongs to the Siberian subtype of Tick-borne encephalitis virus. Comparison of Za virus with two related viruses, a Far Eastern isolate, Sofjin, and a Siberian isolate, Vasilchenko, revealed differences among the three viruses in pathogenicity for Syrian hamsters, cytopathogenicity for PS cells, plaque morphology, and the electrophoretic profiles of virus-specific nonstructural proteins. Comparative amino acid alignments revealed 10 individual amino acid substitutions in the Za virus polyprotein sequence that were different from those of other tick-borne flaviviruses. Notably, the dimeric form of the Za virus NS1 protein migrated in polyacrylamide gels as a heterogeneous group of molecules with a significantly higher electrophoretic mobility than those of the Sofjin and Vasilchenko viruses. Two amino acid substitutions, T277->V and E279->G, within the NS1 dimerization domain are probably responsible for the altered oligomerization of Za virus NS1. These studies suggest that the patient from whom Za virus was isolated died due to increased pathogenicity of the latent virus following spontaneous mutagenesis.

* Corresponding author. Mailing address: CEH Institute of Virology and Environmental Microbiology, Mansfield Rd., Oxford OX1 3SR, United Kingdom. Phone: 44-1865-281632. Fax: 44-1865-281696. E-mail: eag{at}ceh.ac.uk.

Journal of Virology, January 2003, p. 25-36, Vol. 77, No. 1
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.1.25-36.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.





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